Galanin is a 30 amino acid neuropeptide in humans (29 amino acids in rodents) that is widely distributed in tissues including brain, spinal cord, and gut (1). Galanin regulates numerous processes including nociception, nerve regeneration, feeding, memory, neuroendocrine release, gut secretion and contractility (2,3). Three galanin receptor subtypes (GalR1, GalR2, and GalR3) have been cloned and belong to the superfamily of G protein-coupled 7-transmembrane receptors (4,5). These receptors have been shown to couple to various G-protein systems that modulate second messenger activity. Galanin stimulation of GalR1 is sensitive to pertussis toxin, consistent with coupling to Gi/o-type G proteins (6).
All three galanin receptor subtypes are expressed in the dorsal root ganglia (DRG) and the spinal cord (7). The anatomical location of both galanin and its receptors, and the upregulation of galanin in response to nerve damage suggests that the galanin-GalR pathway may play a key role in the regulation of spinal nociceptive transmission (8-10). Intrathecal dosing of galanin enhanced the spinal anti-nociceptive response to morphine and reduced the physical signs of opiate withdrawal (11, 12). GalR1 may be a key galanin receptor for anti-nociceptive transmission. Intrathecal administration of a galanin peptide analog with GalR1 selectivity improved pain threshold in a neuropathic pain model (13, 14).
In recent studies, the expression, mitogenic function, and signaling mechanism of GalR1 were investigated in normal and malignant oral epithelial cells. Upon competitive inhibition of GalR1, proliferation was upregulated in immortalized and malignant keratinocytes. Studies also demonstrated that GalR1 inhibits proliferation in immortalized and malignant keratinocytes by inactivating the MAPK pathway. (15)